Throughout this application various references are referred to within parentheses. Disclosures of these publications in their entirety are hereby incorporated by reference into this application to more fully describe the state of the art to which this invention pertains. Full bibliographic citations for these references maybe found at the end of this application, immediately preceding the claims.
Paraneoplastic sensory neuronopathy is a rare remote effect of cancer characterized clinically and pathologically by neuronal loss and inflammatory infiltrates. (1, 6, 7) A high percentage of such patients harbor a characteristic serum antibody which has been called anti-Hu. (4) These sera react with a group of proteins which have been found to be specifically expressed in tumor tissue (usually small cell lung cancer) and brain. (8) This observation suggested a model for the neurological dysfunction in which an immune response primarily directed against a tumor antigen is misdirected against similar antigens expressed in brain. (4, 5) The synthesis of the anti-Hu antibody in the brain and the specific deposits of IgG and infiltrating lymphocytes provide circumstantial evidence for this model.
In addition to their neurological interest these cancer patients are unique in that they make a profound immunological response to their tumor. The mechanisms underlying this specific anti-tumor response are not well understood. It is not because these patients uniquely express the Hu-antigen in their small cell lung tumors. All small cell lung tumors (so far analyzed) express the Hu antigen. There are a number of possible mechanisms; (a) the Hu antigen may be mutated and perceived as foreign, (b) in the individuals the expression of a brain protein in extraneural tissue provokes an extraordinary response, (c) there is an unknown secondary contributing factor e.g., viral infection.
Irrespective of the mechanism involved, the sera of these patients (which contains high-titre anti-Hu IgG) provides a reagent to isolate and characterize human small cell lung cancer tumor antigens.